In this episode of the BroadEye Podcast, hosts Shawn Maloney and Dr. Bruno Fernandes welcome Prof. Michel Michaelides, one of the most active clinical researchers in ophthalmology today. Prof. Michaelides leads a large inherited retinal disease clinic—seeing 30–40 children and adults each week—and splits her time between patient care, advanced imaging research, and steering more than ten ongoing clinical trials.

Why This Matters Inherited retinal diseases affect hundreds of thousands worldwide, and for most there is still no approved treatment. Over the past two years, we’ve seen multiple Phase 1/2 gene-therapy trials move into registrational studies, alongside novel antioxidant approaches and AI-driven biomarkers. Today’s conversation cuts through the jargon to give you a clear picture of where the field stands—and where it’s headed.

Key Takeaways

• Beyond RPE65: While Luxturna paved the way, newer AAV-based therapies for X-linked RP (RPGR) and other targets are now in Phase 2 and Phase 3 trials, with early data showing promising safety and efficacy.

• Imaging & Function: Prof. Michaelides is pioneering next-generation retinal imaging devices and novel functional assays to capture meaningful changes in vision—critical for shortening trial timelines.

• Antioxidant Strategies: High-dose N-acetylcysteine trials are under way, offering a non-viral approach to slow photoreceptor degeneration across multiple genetic subtypes.

• AI in Stratification: Machine-learning algorithms on retinal scans can help predict progression rate and identify the best candidates for specific therapies, improving both trial design and patient outcomes.

• Balancing Dose & Safety: Finding the sweet spot between transgene expression and immune activation remains a core challenge—Prof. Michaelides shares lessons learned from dose-escalation cohorts.

• Phase 3 & Beyond: With over a hundred patients enrolled in pivotal studies, we’re closing in on potential approvals—but long-term follow-up and real-world evidence will determine ultimate impact.

About the Guest Prof. Michelle Michaelides is a clinician-scientist specializing in inherited retinal diseases. She leads dedicated adult and pediatric IRD clinics, oversees the development of advanced imaging and functional biomarkers, and serves as principal investigator on over ten clinical trials spanning gene therapies, antioxidant agents, and AI-guided stratification tools. Prof. Michaelides regularly lectures at international conferences and collaborates with industry and academic partners to accelerate the translation of research into real-world treatments.

In this latest episode of the BroadEye podcast, hosts Shawn Maloney and Dr. Bruno Fernandes sit down with Dr. Arshad M. Khanani, MD, MA, FASRS, a pioneer in vitreoretinal gene-therapy trials and Managing Partner at Sierra Eye Associates. Dr. Khanani shares front-line insights into how genetic medicines are reshaping treatment for inherited and degenerative retinal diseases, highlighting both the promise and the practical challenges of bringing one-time therapies to patients.

Why Gene Therapy Matters Today Recent years have seen the first US approvals of in-vivo retinal gene therapies, beginning with voretigene neparvovec (Luxturna) for RPE65-mediated inherited retinal dystrophy in December 2017. These one-off treatments offer durable vision improvements where none existed before, but they also raise questions of long-term safety, vector delivery, and equitable access.

Dr. Khanani’s Journey With over a decade leading surgical trials in sustained-delivery and viral-vector therapies, Dr. Khanani has overseen early human work on next-generation agents—including subretinal injections of AAV vectors and novel capsid designs. He describes lessons learned from Phase 1 safety studies through global registrational trials, emphasizing iterative “vector evolution” to boost efficacy and minimize inflammation.

Key Takeaways

• Vector Optimization: Directed-evolution platforms are accelerating discovery of capsids that target photoreceptors more precisely, reducing off-target toxicity.

• Durability vs. Dose: Striking the right balance between transgene expression and immune activation remains central—higher doses don’t always equal better outcomes.

• Regulatory Pathways: While Luxturna set a precedent, streamlined FDA and EMA guidance on trial endpoints and real-world evidence will shape the next wave of approvals.

• Cost & Access: Innovative payment models (e.g., outcomes-based installment plans) are emerging to address the multi-hundred-thousand-dollar price tags of these therapies.

About the Guest Dr. Arshad M. Khanani, MD, MA, FASRS, is a vitreoretinal surgeon, researcher, and Managing Partner at Sierra Eye Associates in Reno, Nevada. He holds dual degrees in medicine and medical humanities from the University of Nevada, Reno, and is a fellow of the American Society of Retina Specialists. Dr. Khanani has authored over 100 peer-reviewed articles on retinal disease and served as principal investigator on more than 30 clinical trials of gene and cell therapies for inherited and age-related retinal disorders. He also lectures internationally on surgical innovation, vector design, and the economics of advanced ocular treatments.

In this episode of the BroadEYE Podcast, hosts Shawn Maloney and Dr. Bruno Fernandez dive into a fascinating discussion with Dr. Peter Campochiaro, a clinician-scientist at Johns Hopkins’ Wilmer Eye Institute, about the potential of N-acetylcysteine (NAC) as a treatment for retinitis pigmentosa (RP).

Dr. Campochiaro shares how his research journey began with unexpected findings in mouse models, revealing how excess oxygen in the retina—caused by the loss of rod photoreceptors in RP—leads to oxidative stress that damages surviving cone cells. This discovery paved the way for the NAC Attack clinical trial, a phase 3 study exploring whether NAC, a potent antioxidant, can slow cone degeneration and preserve vision in RP patients.

The conversation covers the science behind NAC, its safety profile, and why it was chosen over other antioxidants like glutathione or CoQ10. Shawn, who lives with late-stage RP, brings a personal perspective, while Bruno, an ophthalmologist, digs into the broader implications for retinal diseases. Dr. Campochiaro also addresses practical challenges, like NAC’s over-the-counter availability versus its regulated use, and cautions against self-medication without medical supervision.

The episode offers hope for RP patients while emphasizing the importance of awaiting trial results, expected in a couple of years, to confirm NAC’s efficacy and long-term safety.

In this episode, we sit down with Angela Bonfanti, the first female CEO and President of the Canadian National Institute for the Blind (CNIB). Angela shares her personal and professional journey, the challenges and opportunities of leading a 106-year-old organization, and her vision for improving accessibility and inclusion for individuals with vision loss in Canada.

Angela Bonfanti, the CEO and President of CNIB, is a trailblazer in the accessibility and inclusion space. With over 13 years of dedicated service at CNIB in various leadership roles, Angela became the organization’s leader in 2023, marking her 13th anniversary with the institute. She brings a deeply personal connection to her work, having grown up witnessing her father's journey with vision loss due to Retinitis Pigmentosa. Angela's leadership is defined by her commitment to systemic change, grassroots advocacy, and empowering individuals with vision loss through innovative programs and community-driven solutions.

The Canadian National Institute for the Blind (CNIB) is Canada’s leading organization dedicated to empowering people impacted by blindness and vision loss. Established in 1918, CNIB supports individuals across the country with programs focusing on education, employment, accessibility, and advocacy. From guide dog training to groundbreaking virtual services, CNIB aims to create a world without barriers for people living with vision loss. Under Angela Bonfanti's leadership, the CNIB continues to advance its mission of inclusivity and accessibility through collaboration and innovative strategies.

Dr. Carlos Quezada-Ruiz is a Vitreoretinal Surgeon and Assistant Professor of Ophthalmology at the Instituto de Oftalmologia Fundación Conde de Valenciana’s Retina Department in Mexico City. He also serves as the Senior Vice President of Clinical Research and Development and Therapeutic Area Head (Ophthalmology) at 4DMT, leading early- and late-stage clinical development teams focused on treating neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and geographic atrophy (GA).

In addition to his active clinical practice, Dr. Quezada-Ruiz has spent the past decade as a Drug Developer, beginning at Genentech–Roche. There, he worked on the Ophthalmology management team as Group Medical Director of Clinical Science (Product Development). During his tenure, he led the design, execution, and analysis of U.S. and global registrational trials for multiple retinal diseases, including the nAMD global clinical development program for VABYSMO, resulting in U.S. and worldwide approvals. He also led the global clinical science team for SUSVIMO, supporting its initial global filing, FDA approval, and launch in nAMD; successfully navigated the U.S. voluntary recall and commercial relaunch; and oversaw the phase 3 DR/DME registrational program through execution, readout, and filing with the FDA in early 2024. Previously, Dr. Quezada-Ruiz led Medical Affairs efforts for the U.S. launch of Lucentis Prefilled Syringe (PFS) and the myopic choroidal neovascularization indication for LUCENTIS.

Furthermore, Dr. Quezada-Ruiz contributed to diversity and inclusion strategies in the Ophthalmology Franchise—such as the AAO MOM program—and advanced personalized healthcare in retina at Genentech by helping design and develop predictive models that use machine learning and large language models to support both drug development and clinical practice.

Dr. Quezada-Ruiz is a Fellow of the American Society of Retina Specialists, with over 13 years of clinical practice and research in vitreoretinal diseases and surgery. He earned his M.D. from Universidad Autónoma de Coahuila in his hometown of Torreón, Mexico. He completed fellowships in Vitreoretinal Surgery, Ocular Pathology Research, and Vitreoretinal Surgery Research at Universidad Nacional Autónoma de México, McGill University, and the California Retina Research Foundation, respectively. In 2023, he completed an Executive Education program (CIBE) at Columbia Business School.

His accolades include the 2023 Roche Award of Excellence in recognition of outstanding contributions to Roche Pharmaceuticals (“Vabysmo and Beyond”), Genentech’s 2023 Medical Excellence Award, the 2019 American Society of Retina Specialists Senior Honor Award, the 2016 ASRS Honor Award, the 2013 Gillingham Pan-American Fellowship by the Pan-American Association of Ophthalmology and The Retina Research Foundation of Houston, Texas, and the 2013 Leonard Ellen Ocular Pathology Award by the Royal Victoria Hospital Foundation.

On a personal note, Dr. Quezada-Ruiz is married to Cecy—formerly a marketing specialist at The Coca-Cola Company—and they have three children and a white Labrador, Mia, who is blind from retinal dystrophy. He is also a retired martial artist, philosopher, and health enthusiast.

About 4DMT 4DMT is a clinical-stage genetic medicines company focused on harnessing the full potential of genetic therapies for large market diseases, particularly in ophthalmology (wet AMD and DME) and pulmonology (cystic fibrosis lung disease).

Therapeutic Vector Evolution (TVE): 4DMT’s proprietary vector platform leverages the Nobel Prize–winning technology of directed evolution to create customized viral vectors. This approach propels a diverse product pipeline aimed at revolutionizing medicine with potentially curative therapies for millions of patients.

In this episode, we sit down with Jason Menzo, CEO of the Foundation Fighting Blindness, to discuss his unique journey from the pharmaceutical industry to leading one of the world’s most impactful organizations in eye health. Jason shares insights on his career transition into the nonprofit sector and his commitment to advancing the Foundation’s mission. We explore groundbreaking initiatives like My Retina Tracker, a resource bridging patients to clinical trials, and dive into the Foundation’s bold vision for future treatments, including the potential of eye transplants. Plus, hear how the Foundation is fueling innovation by investing in promising small eye care companies and funding research to combat inherited retinal diseases.